The epidemic of childhood obesity has led to the emergence of a cluster of cardiovascular risk factors, known as the metabolic syndrome, in nearly 9 percent of US teens;This K23 award investigates the development of the metabolic syndrome among early adolescents, with a focus on the mechanism of changes in adiponectin levels and visceral fat in relation to tobacco exposure, building on previous publications and pilot studies. The proposal provides Dr. Cook with a rigorous didactic and mentored training program in clinical research, focusing on the development during adolescence of the metabolic syndrome and its components. The didactic curriculum includes targeted training in courses, seminars and two offsite training programs, providing background and experience that bridge basic and clinical research. Dr. Cook : will obtain essential clinical research experience by conducting 2 interlocking projects under the guidance of an experienced, multi-disciplinary mentoring team. The overarching theme of the.research plan is to study precursors of obesity, diabetes, and cardiovascular risk factors during adolescence. During this critical biological period of physiologic change in body composition and insulin resistance, an individual establishes lifelong habits of diet, activity, and tobacco .use. Study 1 will build and follow a community cohort of above- average-weight 9-10 yr olds with various degrees of household smoke exposure. Cotinine, a metabolite of nicotine, will be used to quantify and track duration of tobacco exposure. This study will examine] longitudinal changes in key factors, such as adiponectin and total/central body fat, in relation to tobacco exposure during the critical period of puberty. These analyses may identify precursors to changes in the cardiovascular risk factors of the metabolic syndrome (dyslipidemia, elevated blood pressure, impaired glucose/insulin metabolism). Study 2 will be a cross-sectional metabolic substudy of subjects recruited from the larger cohort in Study 1, including individuals with high smoke exposure (passive of actiive) and no smoke exposure. They will undergo MR! for visceral fat measurement and a frequently sampled glucose tolerance test to determine insulin resistance. Ultimately, we propose to test the hypothesis that adolescence is a vulnerable period that stabjishes the course of future cardiovascular disease in adults, /^better understanding of early stages of cardiovascular disease will allow us to optimize both prevention and intervention strategies in future studies. (End of Abstract)